NEW YORK (GenomeWeb) – Looking to bring its colorectal cancer panel to market as quickly as possible, Applied Proteomics is developing an ELISA version of the diagnostic that it plans to offer as a laboratory-developed test aimed at assessing cancer risk in patients with gastrointestinal symptoms.
The company had previously planned to bring the test to market on a multiple-reaction mass spectrometry platform, placing it at the vanguard of mass spec-based clinical proteomics. According to John Blume, API's chief science officer, the firm still plans down the road to bring tests to market using mass spec.
"The future of this space is definitely mass spec," Blume told GenomeWeb, noting that he and API believed mass spec would become the technology of choice as the diagnostics field moves towards more highly multiplexed proteomic tests.
"We believe that the era of single protein diagnostics is over," he said. "And when you really get to the requirements that are necessary for [high] sensitivity and specificity for some of these [complex] diseases, it is going to be panels of 30 or 40 proteins. And mass spec is still at the end of the day the best way to measure many things at one time cheaply and rapidly."
However, Blume said, API found in its development efforts that a lead panel of eight proteins was effective at identifying patients at relative risk of having colorectal cancer. And given the smaller than expected size of the panel and the fact that reagents already existed for these eight proteins, the company decided to prep an ELISA version of the test for launch.
"We decided that in order to be aggressive about going to market, we would launch with … just the ELISA version of the test, and in the background work on converting it to a multiplex platform," Blume said, noting that this future multiplex platform could be either a mass spec system or a multiplex immunoassay platform such as those offer by Meso Scale Discovery.
The eight protein panel emerged from two validation studies — one a 274-patient mass spec-based study and the other a 300-patient study using multiplexed immunoassays — evaluating 187 candidate proteins for detection of CRC and advanced adenoma.
"Frankly, we thought we were going to be playing with panels of 20 or 30 or so," Blume said. "So we were pleasantly surprised when it turned out that of the five panels that we validated there that some of them were small enough that we could go with existing reagents on existing platforms."
Blume said the company has an internal timeline set for launch of the test, but he declined to share it.
API ultimately aims to develop a screening test for use in assessing advanced adenoma and colorectal cancer risk in the general population with the goal of improving patient compliance with guidelines on colonoscopies. However, this initial release, Blume said, will target symptomatic patients, helping doctors decide whether to pass them on for a colonoscopy.
"There are patients who go to the doctor and have no clear pathology that is observable but have symptoms that say there is something wrong with their GI tract, and at the moment a lot of these patients get referred to colonoscopy," he said. "So you can imagine that this [test] is another tool that doctors can use for [assessing such] patients."
API will offer this initial version of the test as an LDT. Commercialization of a general screening test, on the other hand, will likely require development of an in vitro diagnostic cleared by the US Food and Drug Administration, Blume said. "For a screening test, and getting something like a national coverage decision, you probably need to go all the way through to an IVD."
Such an effort will also involve a very large study in the test's intended use population, Blume said, adding that it is in the company's "five-year plan" to do that.
Assuming API does develop a mass spec-based FDA-cleared IVD version of the test, it would be moving into uncharted territory in taking such a panel through the agency clearance process. Integrated Diagnostics brought a multiplex mass spec-based proteomic test to market with the launch of its Xpresys Lung panel in 2013, but the company has not taken that product through FDA, offering it instead as an LDT out of its CLIA lab.
Diagnostics company Biodesix is in the process of submitting its Veristrat proteomic lung cancer test to FDA through the PMA process. The Veristrat test is MALDI-TOF based, and Biodesix will most likely submit the test on Bruker's Microflex LT MALDI instrument, which has received FDA 510(k) clearance as part of Bruker's MALDI Biotyper clinical microbiology platform.
One challenge Biodesix faces in preparation for its PMA submission is nailing down the specific peptides underlying the Veristrat signatures. The test has traditionally relied on differentiating between the mass spectra of different clinical samples as opposed to identifying and quantifying specific, known protein analytes, and, in the past, Biodesix has acknowledged that it has not identified all the analytes underlying the spectra generated by the test.
This won't be an issue for API, which uses measurement of specific proteins via multiple-reaction monitoring mass spec on a triple quadrupole for its targeted work and would, presumably, use a similar setup for clinical versions of its panels.
API has been developing its clinical mass spec platform in collaboration with Agilent, which has been at the forefront of the move toward clinical mass spec, collaborating on assay development with proteomic firms including Indi and Sera Prognostics.
In 2013, API inked an agreement with Agilent for a collaboration on clinical MRM mass spec assays and workflows. That deal called for the two companies to develop a commercial version of API's colon polyp/adenoma panel using Agilent's 6490 triple quadrupole, 1290 Infinity LC, RapidFire 360 MS, and Bravo liquid handling systems.